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Food consumption remains the commonest pathway through which humans ingest higher levels of mercury (Hg). Long-term exposure to Hg through Hg-contaminated food may result in acute or chronic Hg toxicity. Incessant discharge of Hg waste from ASGM facilities into nearby farms contaminates food crops. Ingestion of such food crops by residents may lead to detrimental human health effects. The human health risks upon exposure to total mercury (THg) and methylmercury (MeHg) in farmland soils and plantains from farms sited near ASGM facilities were studied in four communities around Obuasi, Ghana. The human health risk assessment was evaluated using hazard quotient (HQ), estimated average daily intake (e AvDI), hazard index (HI) and Hg elimination and retention kinetics. Tweapease, Nyamebekyere and Ahansonyewodea had HQ, e AvDI and HI for THg of plantains for both adults and children below the recommended USEPA limit of 1, 3 × 10-4 mg/kg/day and 1, respectively. Odumase had HQ, e AvDI and HI for THg of plantains for both adults and children, higher than the guideline values. This meant that only Odumase may cause non-carcinogenic human health effects upon repeated exposure. The HQ, e AvDI and HI values of MeHg for all the study areas were far below guideline values, hence may not pose any non-carcinogenic human health risks to residents even upon repeated exposure. Retention and elimination kinetics of Hg also showed that only plantains from Odumase may pose significant non-carcinogenic human health risks to residents because the final amount of inorganic mercury exceeded the extrapolated USEPA guideline value of 0.393 μg/kg/year.

Novel lactate (LA)-based polymers containing medium-chain-length 3-hydroxyalkanoates (MCL-3HA) were produced in fadR-deficient Escherichia coli strains from glucose as the sole carbon source. The genes encoding LA and 3-hydroxybutyrate (3HB) monomers supplying enzymes [propionyl-CoA transferase (PCT), d -lactate dehydrogenase (D-LDH), β-ketothiolase (PhaA), and NADPH-dependent acetoacetyl-CoA reductase (PhaB)], MCL-3HA monomers supplying enzymes [(R)-3-hydroxyacyl-ACP thioesterase (PhaG) and (R)-3-hydroxyacyl (3HA)-CoA ligase] via fatty acid biosynthesis pathway, and modified polyhydroxyalkanoate (PHA) synthase [PhaC1(STQK)] of Pseudomonas sp. 61-3 were introduced into E. coli LS5218. This resulted in the synthesis of a novel LA-based copolymer, P(LA-co-3HB-co-3HA). 1H-nuclear magnetic resonance (NMR) analysis revealed the composition of P(LA-co-3HB-co-3HA) to be 19.7 mol% LA (C3), 74.9 mol% 3HB (C4), and 5.4 mol% MCL-3HA units of C8 and C10. Furthermore, the recombinant E. coli CAG18497 strain carrying these genes, excluding the phaAB genes, accumulated P(92.0% LA-co-3HA) with a novel monomer composition containing C3, C8, C10, and C12. 13C-NMR analysis showed the existence of LA-3HA sequence in the polymer. The solvent cast film of P(92.0% LA-co-3HA) exhibited transparency similar to poly(lactic acid).

Frequent discharge of mercury waste from artisanal and small-scale gold mining (ASGM) facilities into nearby farms may contaminate foodstuffs and the entire farms. High contamination levels may result in ecological risks to the soil, plants, animals, humans, and the entire farm ecosystem. This original research is the first study within the catchment areas that describes the effects of mercury waste on the entire farm ecosystem. In this study, the contamination levels and the associated ecological risks of farmland soils, plantains, and cassavas from farms sited near ASGM facilities in four communities around Obuasi, Ghana, were evaluated using the Hakanson (1980) model. Results showed that all samples except for the edible parts of plantains from Tweapease, Nyamebekyere, and Ahansonyewodea and plantain peels from Nyamebekyere and Ahansonyewodea were contaminated and may pose moderate to very high ecological risks. All farms were also contaminated and may pose considerable to very high ecological risks. The farms at Odumase were the highest contaminated with degree of contamination (C

Olfactory neuroblastoma (ONB) is a relatively rare nasal or paranasal malignant tumor. This tumor is rarely accompanied by paraneoplastic syndromes such as syndrome of inappropriate antidiuretic hormone secretion (SIADH). Here, we report a 31-year-old female with histologically confirmed ONB who had been diagnosed with SIADH three years prior. She was treated with surgery followed by concurrent chemoradiotherapy. SIADH resolved immediately after surgical tumor resection. Immunohistochemically, both biopsy and resected specimens from the nasal cavity had been negative for ADH. Although extremely rare, ONB may be associated with SIADH, and the possibility of this cancer should be taken into account during the follow-up of idiopathic SIADH.

Combined small cell carcinoma (SCC) and squamous cell carcinoma (SqCC) of the oropharynx is extremely rare and shows an aggressive clinical course. There are only 5 reported cases of combined SCC and SqCC in the English language literature. Here, we report a 59-year-old male presenting with a right tonsillar mass. The mass was biopsied, and the histological findings showed a proliferation of small-sized tumor cells with scant cytoplasm. Immunohistochemically, the tumor cells were positive for neuroendocrine markers (synaptophysin, chromogranin A, and CD56). Our first diagnosis was tonsillar small cell carcinoma. We treated the patient with concurrent chemoradiotherapy together with cisplatin followed by surgery. The resected tonsillar specimen showed a residual tumor composed of SCC and SqCC, and lymph nodes showed metastatic tumor cells of the SCC component. Immunohistochemically, the SCC component was positive for all neuroendocrine markers and p16; on the other hand, the SqCC component was positive for p40, p63, p16, and EGFR. Fluorescence in situ hybridization revealed that neither component showed any EGFR gene copy number gain. The patient was treated with adjuvant chemotherapy consisting of irinotecan and cisplatin. Liver and bone metastases developed, resulting in the death of the patient. We discuss the present case and review similar cases. Most cases of combined SCC and SqCC occur regardless of p16 status, and a therapeutic strategy has yet to be determined. Further examination of this kind of combined tumor is necessary.

Background Inflammatory pseudotumor (IPT) is a tumefactive lesion characterized by fibroblastic proliferations and a prominent inflammatory component. It behaves as a locally benign or aggressive lesion, clinically and radiologically mimicking a neoplastic process. Numerous entities can be diagnosed as IPT, from reactive lesions to true neoplasms. The diagnosis of IPT requires further elaboration, and IPT should be distinguished from other similar entities such as inflammatory myofibroblastic tumor and IgG4-related sclerosing disease. Case summary We report two cases of IPT arising from the head and neck region. One occurred at the orbit and the other at the parapharyngeal space. Histologically, they showed aggregates of myofibroblasts and inflammatory cells. Immunohistochemically, the number of IgG4-positive cells was less than 40% of the number of IgG positive cells, and the myofibroblastic cells were negative for anaplastic lymphoma kinase. The diagnosis was IPT/not otherwise specified. One patient was treated by systemic administration of corticosteroid and had good response. The other, who was treated by local administration of corticosteroid, partially responded and is currently stable with limited disease. Discussion IPT has been reported to occur in various anatomical sites, most commonly in the lungs. The incidence in the head and neck area is extremely rare. Treatment of IPT is controversial and may involve corticosteroids or surgical resection, or both. Other chemotherapeutic agents and radiotherapy may be considered in steroid-resistant patients. The pathological subtype, safety of resection, and safety of corticosteroid use must be included in the decision-making process for treatment.

Aims In this study, we aimed to investigate the molecular mechanisms underlying the development of mucoepidermoid carcinoma (MEC). Methods and results In 31 cases, we examined the MAML2 fusion status using reverse transcriptase–polymerase chain reaction, and HER2 and EGFR status using immunohistochemistry and chromogenic in-situ hybridization. MAML2 fusions were detected in 15 (57.7%) of 26 MECs analysed, including 11 of 16 (68.8%) low-grade, two of four (50%) intermediate-grade and two of six (33.3%) high-grade MECs. HER2 gene amplification and an increased EGFR gene copy number (with balanced chromosome 7 high-polysomy) were each detected in four of 28 (14.3%) MECs analysed. Irrespective of MAML2 fusion status, all seven high-grade MECs had an increased gene copy number of either HER2 or EGFR, in a mutually exclusive manner, whereas such abnormalities were extremely rare in low- and intermediate-grade MEC. Conclusions These results suggest that HER2 or EGFR gene abnormality could play an important role in the development of high-grade MEC, and also in the progression from MAML2 fusion-positive low-/intermediate-grade to high-grade in a subset of MEC. Furthermore, we suggest that high-grade MEC comprises a heterogeneous group of tumours in terms of molecular pathogenesis, in particular MAML2 fusion status.

Human-papillomavirus- (HPV-) positive oropharyngeal squamous cell carcinomas (OPSCC) are reported to be more responsive to treatment and to be related to a favorable prognosis compared with non-HPV carcinomas. However, the molecular basis of the responsiveness is unclear. Interferon inducible IFI16, which is implicated in the control of cell growth, apoptosis, angiogenesis, and immunomodulation in various types of cancers, is reported to be frequently expressed in the HPV-positive head and neck SCC and to correlate with a better prognosis. In this study, we hypothesized that HPV related OPSCC expresses IFI16 resulting in favorable prognosis. To clarify the relationship between the prognosis of HPV related OPSCC patients and IFI16 status, we examined immunohistologically the pretreatment specimens of OPSCC for the expression of p16 as a surrogate marker of HPV infection and IFI16. We could not show that the expression of IFI16 is associated with that of p16. There was no significant difference in the survival rate between IFI16 positive and negative groups. Patients with p16 negative tumor exhibited worse survival rate regardless of IFI16 status. In this limited case series, we could not conclude that IFI16 expression is altered in p16 positive OPSCC and that it would be a new predictive marker or a useful therapeutic tool.

Myoepithelioma is a rare tumor, accounting for less than 1.5% of all salivary gland tumors. Generally, this tumor exhibits painless solid mass. We here report an extremely rare case of myoepithelioma with remarkable cystic formation in the parotid gland in an 80-year-old female. In this case, a malignant tumor with cystic formation of the parotid gland was clinically suspected following preoperative imaging examinations. Standard superficial parotidectomy was thus performed under general anesthesia. Histopathologic findings revealed that the tumor consisted of spindle cells, plasmacytoid cells, and epithelioid cells, and remarkable cystic formation was observed. Immunohistochemically, the neoplastic cells were positive for S-100, cytokeratin, vimentin, and calponin. The final histopathologic diagnosis was myoepithelioma. Four years have past after the surgery without recurrence of the tumor.

Spindle-cell carcinoma (SPCC) is a rare tumor that presents biphasic components: squamous-cell carcinoma and sarcomatous features without any differentiation. We present a case of SPCC of the hypopharynx in a 60-year-old man. A well-demarcated mass occupying the hypomesopharynx and presenting a pedunculated appearance was observed originating from the lateral wall of left piriform sinus. High signal intensity on T2-weighted magnetic resonance (MR) images corresponded to the myxoid matrix of the tumor on MR pathologic correlation.

Esophageal cancer is frequently associated with head-and-neck cancer. It is difficult to select treatment modalities for synchronous multiple cancers in the upper aerodigestive tract. A 58-year-old woman had synchronous quintuple cancer of the upper aerodigestive tract and was in a poor nutritional state due to oral pain and dysphagia. Clinical stages of cancer in the oral cavity, hypopharynx, cervical esophagus, middle thoracic esophagus, and lower thoracic esophagus were IVA (cT4a N2b M0), I (cT1 N0 M0), IA (cT1 N0 M0), IA (cT1 N0 M0), and IIA (cT3 N0 M0), respectively. After preoperative chemoradiotherapy, curative resection of oral cavity cancer and a tube jejunostomy were performed. Then, pharyngolaryngectomy, total esophagectomy, and pharyngostomy were performed. Finally, after additional radiotherapy to the oral cavity, pharyngogastrostomy with gastric tube and microvascular anastomosis were performed. The patient achieved oral intake and is in good condition and has at this writing remained recurrence free for 26 months. This report suggests that even if there are multiple cancers, adopting multimodal treatment strategies for controlling each cancer may lead to a chance to obtain a complete cure.

Hashimoto K, Yamamoto H, Shiratsuchi H, Nakashima T, Tamiya S, Nishiyama K, Higaki Y, Komune S, Tsuneyoshi M & Oda Y (2012) Histopathology 60, E131–E142 neu gene amplification in carcinoma ex pleomorphic adenoma in relation to progression and prognosis: a chromogenic in-situ hybridization study Aims: The aim of this study was to investigate the potential role of HER-2/neu in the stepwise progression of carcinoma ex pleomorphic adenoma (CXPA) and to evaluate its prognostic significance in CXPA. Methods and results: We examined HER2 overexpression and HER2 amplification by immunohistochemistry and chromogenic in-situ hybridization in 31 cases of CXPA with ductal differentiation (eight intraductal, five intracapsular, and 18 extracapsular) and seven cases of atypical pleomorphic adenoma (PA). HER2 overexpression and HER2 amplification were found in 17 (54.8%) and 12 (38.7%) of the 31 CXPA cases, respectively. HER2 amplification was more prevalent in extracapsular CXPAs (9/18 cases; 50%) than intracapsular CXPAs (1/5 cases; 20%), intraductal CXPAs (2/8 cases; 25%), or atypical PAs (0/7 case; 0%). The status of HER2 amplification was essentially retained from the intraductal to the extracapsular component in individual extracapsular CXPAs. In addition, HER2 amplification was significantly associated with a worse prognosis (shorter disease-free survival time and shorter overall survival time) among extracapsular CXPAs (each P

多形腺腫由来癌では腺腫被膜を基準とした組織学的進展度が予後因子として有用であることが知られているが，現行のTNM分類において，唾液腺腫瘍のT因子には被膜浸潤の程度は反映されていない。今回，多形腺腫由来癌31例において組織学的進展度を評価し，予後予測因子としての有用性に関してT分類との比較検討を行った。pT1，2症例中25%，50%は組織学的に被膜外浸潤癌であり，それぞれ25%，30%で術後遠隔転移を，25%，20%で腫瘍死を認めた。一方でpT3症例の41.7%は非浸潤癌であり，術後再発転移を認めなかった。さらに腫瘍径や術後治療の有無に関わらず，組織学的進展範囲が微小浸潤までに止まる症例は予後良好であり，全生存率，無再発生存率に関してT分類と比較してより有効に予後を反映していた。多形腺腫由来癌の治療に際しては，組織学的進展度評価に基づいた術後補助療法選択や経過観察が必要であると考えられる。

Esophageal perforation with mediastinal abscess formation is a potentially life-threatening complication after chemoradiotherapy (CRT) in patients with esophageal cancer. We present the case of a 64-year-old woman with cervico-thoracic esophageal cancer who had previously undergone distal gastrectomy. Definitive CRT was initially performed since the patient refused laryngectomy. However, she developed an esophageal fistula and a subsequent cervico-mediastinal abscess, which made oral intake impossible. In order to address the fistula, abscess, and cancer, we decided to perform a staged operation. The patient first underwent total pharyngo-laryngo-esophagectomy and abscess drainage. She next underwent esophageal reconstruction with an ileocolonic conduit through a subcutaneous route. The patient is currently alive and well after surgery. This case suggests that surgical resection may be performed in high-risk patients with cervico-thoracic esophageal cancer via a two-stage operation.

Cancer-to-cancer metastasis into a thyroid neoplasm is an uncommon phenomenon with possible diagnostic difficulties. Here, we describe a case of lung adenocarcinoma metastatic into a follicular variant of papillary thyroid carcinoma (FVPTC). A 60-year-old woman with no prior history of malignant neoplasm presented with a nodule in the right lobe of the thyroid gland, some masses in the left lung were found by radiological examination. Histopathological examination of the thyroidectomy specimen demonstrated two different components of carcinoma in a single thyroid nodule; one was FVPTC and the other was high-grade adenocarcinoma. Although both components shared the TTF-1+/CK7+/CK19+/CK20-/SP-A- immunoprofile, only the former was positive for thyroglobulin, and only the latter was positive for CEA. The epidermal growth factor receptor (EGFR) gene mutation at exon21 (L858R) was present only in the latter. The lung biopsy specimen showed cytological, immunohistochemical, and EGFR genotypic features similar to those of the high-grade adenocarcinoma component of the thyroid nodule. These findings resulted in a reliable diagnosis of lung adenocarcinoma metastasizing into an FVPCT and treatment with EGFR-targeted therapy. These results demonstrate that a panel of immunohistochemical staining and molecular analysis is helpful for both diagnosis and appropriate postoperative treatment for a patient with cancer-to-cancer metastasis.

Pleomorphic adenoma (PA) is known to occasionally progress to carcinoma, but the mechanisms of its malignant transformation have not been fully elucidated. S100P, an EF-hand calcium-binding protein, has recently been proposed as an initiator of carcinogenesis in some kinds of epithelial tumors. In this study, we aimed to elucidate the potential role of S100P in tumorigenesis and stepwise progression of carcinoma ex pleomorphic adenoma (CXPA) with ductal differentiation. In 31 ductal type CXPAs (8 in situ, 5 intracapsular, and 18 extracapsular) and 28 PAs (21 conventional and 7 atypical) of the salivary gland, we examined the protein expression of S100P, androgen receptor (AR), HER2/neu, p53, and Ki-67 by immunohistochemistry. HER2 expression, p53 expression, and the Ki-67 labeling index were higher in CXPAs than in atypical PAs and conventional PAs, whereas the AR expression level was relatively high even in atypical PAs. S100P overexpression was significantly more prevalent in CXPAs (27 cases; 87.1%) than in atypical PAs (2 cases; 28.6%) and conventional PAs (1 case; 4.8%) (P

Intra-arterial (IA) chemotherapy for head and neck cancer is effective and multiple IA concurrent chemoradiation (CCRT) protocols have been reported. However, the role of IA CCRT in the multimodality treatment of head and neck cancer is still controversial. We have treated 5 cases of unresectable T4 maxillary sinus squamous cell carcinoma with IA cisplatin (CDDP) and docetaxel (DOC) and CCRT with oral S-1. We report our experience and the effectiveness and feasibility of this combination as an alternative choice of treatment for inoperable head and neck cancer. The patients received an IA infusion of CDDP (50-70 mg/m(2)) and DOC (50-60 mg/m(2)) through the femoral artery, followed by CCRT with oral S-1. The IA infusion was repeated up to 3 times and the radiation was dosed at up to 60-70 Gy. Complete response was achieved in 4 patients and partial response in one, giving an overall response rate of 100%. The most common grade 3 or 4 toxicities were anorexia (80%), mucositis (80%) and leukopenia (80%), all of which were manageable. CCRT with IA CDDP/DOC and oral S-1 was effective and tolerated. Although preliminary, the response rate encourages further pursuit and definitive evaluation of this combination for the treatment of inoperable advanced head and neck cancer.

Objectives/Hypothesis: Salvage surgery after definitive chemoradiotherapy is often associated with a higher rate of perioperative complications and poor prognosis. The objective of this study is to examine the safety and efficacy of free jejunal transfer after salvage pharyngolaryngectomy for patients with locally recurrent hypopharyngeal carcinoma after definitive chemoradiotherapy. Study Design: A retrospective analysis of patients with advanced hypopharyngeal carcinoma who underwent pharyngolaryngectomy and reconstruction using free jejunum. Methods: Forty patients who underwent pharyngolaryngectomy with jejunal transfer were included in this study. Fourteen patients underwent surgery after definitive chemoradiotherapy (the salvage-surgery group), whereas 26 patients underwent surgery after planned preoperative chemoradiotherapy (the planned-surgery group). The perioperative conditions, mortality, morbidity, functional outcomes, and oncologic outcomes in each group were compared. Results: The patients in the salvage-surgery group lost an average of 9 kg in weight before surgery, which thus indicated a malnourished condition. However, the incidence of all perioperative complications did not differ significantly between the groups. All patients in both groups achieved oral intake without tube feeding, and the intervals to start oral intake were 12.8 days in the salvage-surgery group and 15.6 days in the planned-surgery group, which was not significantly different. The 5-year disease-free survival was 57.1% in the salvage-surgery group and 50.4% in the planned-surgery group, which was not significantly different. Conclusions: Salvage pharyngolaryngectomy and jejunal transfer can be performed safely and reliably for patients with locally recurrent hypopharyngeal carcinoma, and it is an excellent option after a failure of definitive chemoradiotherapy.

東京都内で市販されていた紫サツマイモを原材料に用いた61種の加工食品に含まれる主要な8種のアントシアニンを定量した．紫サツマイモのパウダー，フレークおよび干し芋を分類した一次加工食品（10種）には，主要アントシアニンが，53.22～936.26mg/100gの範囲で含まれていた．紫サツマイモを原材料に用いた清涼飲料水や醸造酢，また醸造酢を原材料とする清涼飲料水を分類した飲料形態の加工食品（13種）には，1.19～131.95mg/100mLの範囲で含まれていた．11種の紫サツマイモ油加工食品（チップス・かりんとう）は，33.00～376.39mg/100gの範囲で主要アントシアニンを含んでいた．紫サツマイモを原材料に用いた洋菓子，和菓子およびジャムを分類した二次加工食品（27種）の主要アントシアニン含量は，1.01～69.75mg/100gの範囲であった．また，紫サツマイモの一次加工食品では10種中9種，飲料では13種中13種，油加工食品では11種中6種，二次加工食品では27種中21種において，ペオニジン系アントシアニンの占める割合が70％以上のアントシアニン組成であり，これら加工食品が「アヤムラサキ」「ムラサキマサリ」を原材料にしていると推定された．一方，シアニジン系アントシアニンを多く含む紫サツマイモ加工食品は，紫サツマイモそのものを加工した食品である油加工食品に多く存在した．

5-Fluorouracil (5-FU) is one of the most widely used chemotherapeutic drugs to treat cancer patients. However, the presence of drug resistant tumor cells may cause a poor response to 5-FU based chemotherapy. Dihydropyrimidine dehydrogenase (DPD) is the rate-limiting enzyme in the degradation of pyrimidine bases and is also responsible for the degradation of 5-FU. In this study, we examined whether DPD expression affects the cytotoxic activity of 5-FU against head and neck squamous cell carcinoma (HNSCC) and the role of DPD in the biological regulation of HNSCC. We constitutively expressed the DPD cDNA in a HNSCC cell line. The effect of DPD expression on in vitro cell growth, cell cycle and 5-FU cytotoxicity was examined. In addition, we also evaluated the association between DPD expression and the proliferation of tumor cells in surgical specimens, and prognosis of the patients with HNSCC. DPD overexpression decreases the cytotoxicity of 5-FU. CDHP, a strong DPD inhibitor, enhances the cytotoxic effect of 5-FU in HNSCC cells in vitro. DPD expression level does not effect cell proliferation and does not seem to have prognostic value in HNSCC. The present results strongly indicate that DPD expression plays an important role in the sensitivity of HNSCC to 5-FU chemotherapy, suggesting the possibility of personalized chemotherapy including the prediction of response and adverse effects.

2000年から2008年までに当科で治療を行った上顎洞扁平上皮癌初発症例32例について臨床的検討を行った。内訳は男性23例，女性9例であった。TNM分類はT2：5例，T3：13例，T4a：12例，T4b：2例であった。治療方針として2000年から2003年までは上顎洞試験開洞のうえ可能な限り腫瘍減量術を行い，浅側頭動脈から5-fluorouracil（5-FU）の持続動注を併用の上放射線治療を行った。この時点で腫瘍の残存が認められる症例については拡大手術を施行し，術後には5-FU静脈注射併用の術後放射線療法を行った。2004年以降は，化学療法の変更点として根治手術不能症例を中心に，Seldinger法によるCisplatin（CDDP），Docetaxel（DOC）動注あるいはS-1併用の放射線治療を導入した。全体の疾患特異的3年生存率は68.3%であった。治療開始時期を2003年までに行った前期症例と2004年以降に行った後期症例に分類すると3年生存率で前期62.5%，後期74.6%であった。化学療法の薬剤，投与法の改良が，拡大手術の減少，予後改善に大きく寄与するものと考えられた。

Objective Eyelid carcinomas are rare, and the management strategy of regional lymph node metastasis linked to eyelid carcinomas has not been standardized to date. The aim of the present study was to analyze the patterns of regional metastasis and to assess the optimal extent of surgical treatment for lymph node metastasis of eyelid carcinoma. Methods This study was a retrospective review of patient data from a single institution. From a series of 268 eyelid carcinomas, we selected the 21 patients with lymph node metastasis, and we analyzed the patterns of lymphatic spread, approach to treatment and outcomes. Results The most common histological type of eyelid carcinoma with regional metastasis was sebaceous carcinoma (17/21, 81.0%). Submandibular area metastases were seen only in the patients with the primary tumor originating in the medial half of the eyelid, but parotid area metastases were seen in both the patients whose tumors had a medial-half origin and those with a lateral-half origin. Although 11 of the 16 patients with parotid-area metastases underwent a tumorectomy or superficial parotidectomy (which resulted in four cases of recurrence in the parotid area), none of the five patients who underwent a total parotidectomy developed parotid-area recurrence. The incidence of regional recurrence of the patients who received adjuvant radiotherapy (14.3%) was lower than that of the patients without adjuvant radiotherapy (57.1%). Conclusion Continued surveillance and optimal management of regional lymph node metastases are important for the control and survival of eyelid carcinomas.

Aims: Nitric oxide (NO), produced by inducible NO synthase (iNOS), has been suggested to cause oxidative stress, leading to 8-hydroxydeoxyguanosine (8-OHdG) accumulation and subsequent transversion mutation of DNA. The aim was to evaluate iNOS expression and the status of oxidative stress in nasopharyngeal carcinoma (NPC). Methods and results: Seventy-three cases of NPC were investigated to examine the immunohistochemical expression of iNOS, 8-OHdG and latent membrane protein-1 (LMP-1) and Epstein–Barr virus-encoded small RNA (EBER) expression using in situ hybridization. iNOS mRNA expression and p53 gene mutations were also assessed. Overexpression of iNOS, LMP-1 and EBER was observed in 62 (84.9%), 28 (38.4%) and 53 (72.6%) cases respectively. p53 gene mutation was found in 10 of 73 (13.7%) cases. Immunohistochemical iNOS expression was associated with the 8-OHdG labelling index, iNOS mRNA expression and p53 gene alteration (P

This report describes a case with the re-growth of a residual recurrence of cholesteatoma in a patient who had previously undergone mastoid obliteration using bone putty. At the first visit to the clinic, his external canal resembled one that had undergone canal wall down surgery and his symptoms resembled a cavity problem. Because this recurrent cholesteatoma showed an unusual development, it was not possible to distinguish the cholesteatoma recurrence and a neoplasm using CT and MRI. Surgical removal of the cholesteatoma was extremely difficult because the obliteration covered most of the surgical landmarks. No continuity was identified between the matrix of the cholesteatoma and the eardrum /external ear canal epithelium. The follow-up CT 2 weeks after the initial surgery revealed a residual mass in the mastoid cavity, which required a second surgery for complete removal. This experience indicated that confirmation of the complete removal of a cholesteatoma matrix is critical before deciding to obliterate the mastoid cavity, and that, it is never easy to determine if the procedure is complete. The goal is pneumatization at the mastoid cavity, thereby making it possible to both confirm the recurrence of the cholesteatoma and allowing surgeons to remove it safely.

Squamous cell carcinoma (SCC) of the external auditory canal (EAC) is rare, usually presents at an advanced stage, and is a more aggressive tumor with poor prognosis. The University of Pittsburgh TNM staging system commonly used in prognostication is not perfect, and more accurate biomarkers predicting prognosis are needed. Tumor budding is an established negative prognostic factor at the invasive front in colorectal cancer. Moreover, immunohistochemical studies showed that laminin 5-γ2 (Ln5-γ2) is expressed at the invasive front in tumor or tumor budding cells. We assessed the prognostic significance of tumor budding and Ln5-γ2 expression by performing Ln5-γ2 immunohistochemistry and evaluated the degree of tumor budding in pre-treatment biopsy specimens, and investigated their correlations to clinicopathological parameters in patients with SCC of the EAC. Patients whose tumors had high budding grade and Ln5-γ2 expression had significantly shorter survival times. Budding grade was significantly correlated with Ln5-γ2 expression. Multivariate analysis revealed that high budding grade predicted poorer prognosis regardless of disease stage. Our results suggested that budding grade and Ln5-γ2 expression can be used as indicators of poor prognosis in patients with SCC of the EAC.

Human papillomavirus (HPV) infection is an indicator of good response to chemoradiotherapy in oropharyngeal squamous cell carcinoma (OPSCC), and epidermal growth factor receptor (EGFR) is a molecular-therapeutic target in head and neck squamous cell carcinoma. Here we investigated the prevalence and prognostic significance of HPV infection and EGFR alteration in OPSCC. We analyzed the presence of high-risk HPV using in situ hybridization, protein expressions of p16 and EGFR using immunohistochemistry, and the EGFR gene copy number gain using chromogenic in situ hybridization (CISH) in 105 cases of OPSCC. The biopsy specimens before chemoradiotherapy were used for these analyses. HPV infection and p16 protein overexpression were detected in 53.3% and 52.4% of the OPSCCs, and each factor was associated with better overall survival (P = .0026 and P = .0026) and nonkeratinizing histology (P = .0002 and P = .0004), respectively. EGFR gene copy number gain (high polysomy or amplification) was detected in 12.4% of the OPSCCs and was correlated with EGFR protein overexpression (P = .0667) and worse overall survival (P < .0001). HPV infection and EGFR gene copy number gain (EGFR CISH positive) were mutually exclusive. The HPV-negative/EGFR CISH-positive OPSCCs had significantly worse overall survival than did the HPV-positive/EGFR CISH-negative OPSCCs and HPV-negative/EGFR CISH-negative OPSCCs (P < .0001 and P < .0001, respectively). The EGFR CISH-negative OPSCCs had favorable prognosis irrespective of HPV infection. Our results suggest that EGFR gene copy number gain-positive tumors represent an HPV-negative, aggressive subgroup of OPSCCs. The molecular subclassification of OPSCCs based on HPV infection and EGFR status may serve as important information for appropriate therapeutic strategy.

Pseudomonas sp. 61-3 accumulates two types of polyhydroxyalkanoates (PHAs), poly(3-hydroxybutyrate) [P(3HB)], and poly(3HB-co-3-hydroxyalkanoates) [P(3HB-co-3HA)], and some proteins associated with their PHA granules have been identified. To date, PhaFPs (GA36) and PhaIPs (GA18) were identified from P(3HB-co-3HA) granules. In this study, the gene encoding GA24 associated with P(3HB) granule was identified as phbPPs. PhbPPs was composed of 192 amino acids with a calculated molecular mass of 20.4 kDa and was assumed to be a phasin. phbFPs gene and unknown ORF were also found on phb locus. PhbFPs was anticipated to be the transcriptional repressor of phbPPs gene. PhbPPs was bound to the P(3HB-co-3HA) granules with 3HB composition of more than 87 mol%, and PhaIPs and PhaFPs were bound to the P(3HB-co-3HA) granules with 3HA (C6–C12) composition of more than 13 mol% in the producing cells, suggesting that localization of these proteins is attributed to the monomer compositions of the copolymers.

Extracts of mulberry fruits (Morus sp.) were prepared from 8 cultivars harvested at 4 stages of maturity, and their radicalscavenging activity, anthocyanin content, and total phenolic content were measured. The radical-scavenging activity was evaluated by a spectrophotometric assay using the 1,1-diphenyl-2-picrylhydrazyl radical (DPPH) in a 96-well microplate. Mulberry fruit extracts exhibited the DPPH-scavenging activities, ranging from 2.5 to 20.3 μmol-Trolox equiv/g-FW. Their activities were variable during maturation, and the highest activity was observed in the fully mature mulberry fruit in all cultivars. Anthocyanin was scarcely present in the immature mulberry fruits; however, its content increased as the fruit matured in all cultivars. On the other hand, all immature mulberry fruits contained non-anthocyanin phenolic compound. An on-line high-performance liquid chromatography (HPLC) method for the detection of DPPH-scavenging compounds revealed the difference in predominant radical scavengers between the immature and fully mature stages in the Miran 5 cultivar. Four major radical scavengers in the Miran 5 cultivar were assigned to 2 caffeoylquinic acids (chlorogenic acid and its isomer) and 2 anthocyanins (cyanidin 3-glucoside and cyanidin 3-rutinoside) in the immature and fully mature stages, respectively, by LC-ESI-MS/MS analysis. The change in the content of 4 compounds in mulberry fruits during maturation demonstrated that the most likely contributors to the DPPH-scavenging activity were caffeoylquinic acids in the immature mulberry and anthocyanins in the mature and fully mature mulberry.

This study investigated hearing levels in cases of intractable otitis media with eosinophils and validated the treatment strategy. Medical charts were reviewed retrospectively. The diagnosis was made when the proportion of eosinophils in middle ear secretions exceeded 10%. Twelve patients were identified and treated with an antihistaminergic agent, leukotriene receptor antagonist and topical steroid. The air-bone conductance gap decreased significantly with the relief of subjective symptoms. Bone conduction hearing levels at 4 and 8 kHz were higher than at lower frequencies. There was a significant correlation between subjective symptom duration and bone conduction hearing level at 8 kHz, which diminished with treatment. Compared with suppurative otitis, active otitis with eosinophilia damages high-tone sensory hearing in a time-dependent manner, and antiallergic treatment prevents progression of the high-tone sensory hearing loss. We emphasize the importance of diagnosis and the validity of treatment for intractable otitis media with eosinophils.

In a recent study, it was reported that 4-methyl-2,4-bis(4-hydroxyphenyl)pent-1-ene (MBP), a metabolite of bisphenol A (BPA; 2,2-bis(4-hydroxyphenyl)propane), showed estrogenic activity in several in vitro assays, and the estrogenic activity of MBP was higher than that of BPA. In this study, we have investigated the early life stage toxicity and estrogenic effect of MBP on medaka (Oryzias latipes). The 96-h median lethal concentration value of MBP and BPA with 24-h-old larvae was estimated to be 1,640 and 13,900 microg/l, respectively. The hatchability of fertilized eggs exposed to MBP and BPA over 14 days was significantly decreased at doses of 2,500 microg/l and 12,500 microg/l, respectively. Moreover, to compare the potency of estrogenic activity in vivo, male medaka were exposed to various concentrations of MBP and BPA for 21 days. The lowest-observed-effect concentrations of MBP and BPA for hepatic vitellogenin induction in male medaka were estimated to be 4.1 and 1,000 microg/l, respectively. These results suggest that MBP has high toxicity for early life stages of the medaka, and that the estrogenic activity of MBP was about 250-fold higher than that of BPA to male medaka.

当科で施行した可動部舌癌に対するpull through手術による摘出，舌再建術後の局所合併症の発生について検討を行なった。1998年から2004年の7年間にpull through手術を行なった可動部舌癌症例52例（23-82歳）を対象とした。術後局所感染の発生は13例（25%）に認めた。術式別には舌半切34%（9例／26例），亜全摘で17%（4例／23例），再建術式別には大胸筋皮弁で33%（5例／18例），遊離腹直筋皮弁で17%（4例／23例），一次縫縮症例で33%（3例／9例）であった。摘出範囲，再建術式，手術時間，術中出血量は局所合併症（感染）の発生率に影響を与えていなかった。術前照射群は術後局所感染発生率が高い傾向にはあったが統計学的な有意差はなかった。死腔の充填，術後の的確なドレーン留置，術後の安静など手術手技，周術期管理が大切であることが示唆された。

We investigated the effects of nonylphenol (NP) and triclosan (TCS) on production of vitellogenin (Vg), testosterone (T), and hepatic cytochrome P450 1A and 2B activities in male South African clawed frogs (Xenopus laevis). In a 14-d waterborne exposure test, no significant differences in the level of plasma Vg synthesis in male frogs were observed among the control, 10, 50, and 100 microg/l NP and 20, 100, and 200 microg/l TCS treatment groups. Intraperitoneal injection of male frogs with 2, 20, and 200 microg/g body weight NP resulted in no significant differences in plasma Vg levels among the control and all treatment groups. However, the levels of plasma Vg in all TCS treatment groups (intraperitoneal injection of 4, 40, and 400 microg/g body weight) were lower than that in the solvent control group, and male frogs injected with high doses of NP or TCS had lower T levels than the control group. No significant differences in hepatic cytochrome P450 1A and 2B activities were observed among the all treatment groups. Male frogs injected with 20 microg/g body weight of estradiol-17beta had significantly higher plasma Vg levels than the control group. These results suggest that profiles of plasma Vg and T production in male Xenopus laevis could be useful biomarkers for detecting hormonally active agents.

Triclosan (2,4,4'-trichloro-2'-hydroxydiphenyl ether) is widely used as antibacterial agent in various industrial products, such as textile goods, soap, shampoo, liquid toothpaste and cosmetics, and often detected in wastewater effluent. In this study, the effects of TCS on the early life stages and reproduction of medaka (Oryzias latipes) were investigated. The 96-h median lethal concentration value of TCS for 24-h-old larvae was 602 microg/l. The hatchability and time to hatching in fertilized eggs exposed to 313 microg/l TCS for 14 days were significantly decreased and delayed, respectively. An assessment of the effects of a TCS 21-day exposure period on the reproduction of paired medaka showed no significant differences in the number of eggs produced and fertility among the control and 20, 100 and 200 microg/l TCS treatment groups. However, concentrations of hepatic vitellogenin were increased significantly in males treated with TCS at 20 and 100 microg/l. In the F(1) generations, although the hatching of embryos in the 20 microg/l treatment showed adverse effects, there was no dose-response relationship between hatchability and TCS treatment levels. These results suggest that TCS has high toxicity on the early life stages of medaka, and that the metabolite of TCS may be a weak estrogenic compound with the potential to induce vitellogenin in male medaka but with no adverse effect on reproductive success and offspring.

Background. Although sinonasal inverted papilloma (IP) is a rare benign tumor, it has a tendency to recur and is sometimes associated with squamous cell carcinoma (SCC). Therefore, postoperative long-term follow-up of these patients is recommended. We previously reported that serum SCC antigen might be a useful tumor marker for sinonasal IP. In this study, we investigated whether serum SCC antigen level has a correlation with disease status and is useful in the early detection of recurrent disease. Methods. Blood samples for the analysis of serum SCC antigen were taken from 28 IP patients before and after surgical treatment. Results. Twenty-five (89%) of 28 cases showed evaluated serum SCC antigen levels above the upper limit. This marker level decreased in all cases after surgical resection. Four of these patients had a recurrence. None of the patients with recurrent tumor showed symptoms at the time of detection of their recurrent tumor, and recurrence was discovered from elevated levels of SCC antigen. Conclusions. Serum SCC antigen level has a correlation with disease status of IP and has a potential to serve as a useful tool for monitoring the course of disease. SCC antigen is a reliable tumor marker in the management of sinonasal IPs. © 2004 Wiley Periodicals, Inc. Head Neck27: 44–48, 2005

BACKGROUND: Synovial sarcoma, generally known as a soft tissue tumor, can also occur in the head and neck region, including the thyroid gland. Cytologic findings are important to differentiate the tumor from other types of neoplasms arising in the thyroid gland. CASE: A 60-year-old man complained of hoarseness. A palpable neck tumor was detected, and a computed tomography scan showed a thyroid tumor accompanied by destruction of the thyroid and cricoid cartilage. The results of a preoperative fine needle aspiration biopsy showed numerous spindle cells with pale cytoplasm and oval nuclei with fine, granular chromatin, all of which suggested a medullary carcinoma. The extirpated thyroid tissue weighed approximate' ly 120 g, and a grayish white, elastic, solid tumor (6.8 × 6.5 cm) was present in the left lobe. Histologically, fasciculation of spindle cells that had proliferated solidly and densely was observed. Also, the expression of a chimera gene, SYT-SSX, was detected in the tumor tissue. CONCLUSION: Synovial sarcoma of the thyroid is extremely rare, and its diagnosis by fine needle aspiration biopsy is generally considered very difficult. The detailed cytologic findings observed here might be helpful with the differential diagnosis of thyroid neoplasms.

Thyroid carcinomas with massive intralumen invasion of the great veins are extremely rare and reported to have poor prognosis. We report a case of a poorly differentiated follicular carcinoma of the thyroid with extensive invasion into the bilateral internal jugular veins, brachiocephalic vein, and superior vena cava. All of the seven major drainage veins from the thyroid were involved by tumor thrombus. The patient was successfully treated by surgical resection including removal of the tumor thrombus and repair of the great veins. The importance of preoperative radiological findings, treatment, and outcome are discussed along with a literature review.

Aims: Only a few reports on renal cell carcinoma with rhabdoid features have been published. This study was performed to investigate the clinicopathological characteristics of renal cell carcinomas with rhabdoid features. Methods and results: Among 253 cases of renal cell carcinoma in adults, eight cases with rhabdoid features were detected. Rhabdoid areas ranged from 10% to 90% of each of the cases. Seven of the eight cases were TNM stage III or IV, and four of the eight cases died within 8 months of surgery. Immunohistochemically, the rhabdoid areas were positive for CAM 5.2 (4/8), AE1/AE3 (6/8), epithelial membrane antigen (6/8) and vimentin (8/8), and negative for myogenetic markers (0/8). The mean MIB-1 labelling index in the rhabdoid areas was higher than that in the definite carcinomatous areas. Ultrastructurally, perinuclear whorls of intermediate filaments were demonstrated in three of the eight cases using paraffin-embedded blocks. Conclusions: The rhabdoid areas in renal cell carcinoma have histological, immunohistochemical and ultrastructural similarities to malignant rhabdoid tumours. Renal cell carcinoma with rhabdoid features is a highly aggressive neoplasm and its malignant behaviour may be due to the high cell-proliferative activity of the rhabdoid areas. Rhabdoid features in renal cell carcinoma may represent the endpoint of clonal evolution of renal cell carcinoma (especially in clear cell type cases).

The rhabdoid cell, which is typically observed in malignant rhabdoid tumor (MRT) and other malignant neoplasms, has an eosinophilic cytoplasm containing a spheroid perinuclear inclusion body. This distinct cell is known to act as a highly aggressive indicator in many types of malignant tumors and is characterized by aggregates of intermediate filaments, comprising both vimentin and cytokeratin (CK) 8, which is mainly expressed in simple-type epithelium such as liver and intestine. To clarify the cause of the inclusion body formation, we analyzed the alteration of the complete human CK8 gene (KRT 8: 1724 base pairs) in seven samples of MRT (three from frozen materials and four from cultured cell lines) by reverse-transcriptase polymerase chain reaction, followed by direct sequencing. In addition, the two cell lines, Huh7 and HeLa, which lacked rhabdoid feature, six pediatric malignant tumors, including three cases of primitive neuroectodermal tumor (PNET) and three of Wilms' tumor; and 15 normal liver tissue (as a control) were also analyzed. All MRT samples had missense mutations in the human KRT 8 gene, i.e., Arg89 --Cys (5/7); Arg --Cys251 (3/7); Glu267 --Lys (6/7); Ser290 --Ile, Met; (7/7) and Arg301 --His(4/7), none of which was detected in any control samples. Among these mutations, the most noteworthy findings were that Arg89 belongs to the H1 subdomain of the head domain and that Arg251 belongs to the short nonhelical linker segment, or L1-2. Both these mutations are noted for their relationships to lateral protofilament-protofilament interactions. In addition, Ser290 has been previously reported to be a phosphorylation site, which has been recognized to play an important role in filament organization, leading to conformational change of the CK8 filaments. In conclusion, mutated codons of CK8 gene in MRT were located in the important region involved in the conformational change of intermediate filament.

Hyalinizing clear cell carcinoma (HCCC) is a low-grade salivary gland carcinoma characterized by clear cells and hyalinized stroma. Recently, the EWSR1-ATF1 fusion gene was found in HCCCs. We herein describe three cases of HCCC identified in one male and two females, ranging in age from 27 to 67 years. The tumors were located in the root of tongue, nasopharynx, and soft palate. They were composed of nested or cord-like proliferations of epithelial cells with clear to pale eosinophilic cytoplasm, embedded in hyalinized and focally fibroedematous stroma. Tumor-associated lymphoid proliferation and pseudoepitheliomatous hyperplasia were also observed in each one case. MAML2 fusions specific to mucoepidermoid carcinoma were not detected in any of the three cases. We found EWSR1-ATF1 in two of three HCCCs using reverse transcription polymerase chain reaction (RT-PCR) with our original primer sets designed to detect the fusion gene transcripts in formalin-fixed paraffin-embedded (FFPE) tissues. EWSR1 rearrangement was also confirmed by fluorescence in situ hybridization (FISH) on FFPE sections in two cases. There was a good concordance between the two methods (two positive cases and one negative case by both RT-PCR and FISH). Therefore, RT-PCR and FISH using FFPE tissue may be ancillary tools to confirm the diagnosis of HCCC.

Objectives Kuttner tumour (KT), so-called chronic sclerosing sialoadenitis, is characterised by concomitant swelling of the submandibular glands secondary to strong lymphocytic infiltration and fibrosis independent of sialolith formation. However, recent studies have indicated that some patients with KT develop high serum levels of IgG4 and infiltration of IgG4-positive plasma cells, namely IgG4-related dacryoadenitis and sialoadenitis (IgG4-DS), so-called Mikulicz's disease. The aim of this study was to clarify the clinical and pathological associations between KT and IgG4-DS. Materials and Methods Fifty-four patients pathologically diagnosed with KT or chronic sialoadenitis were divided into two groups according to the presence or absence of sialolith (KT-S (+) or KT-S (−), respectively). Results There were no significant differences in the clinical findings, including the mean age, sex and disease duration, between the two groups. All patients in the KT-S (+) group showed unilateral swelling without infiltration of IgG4-positive plasma cells or a history of other IgG4-related diseases (IgG4-RD), while those in the KT-S (−) group showed bilateral swelling (37.5%), strong infiltration of IgG4-positive plasma cells (87.5%) and a history of other IgG4-RD (12.5%). Conclusions These results suggest an association between the pathogeneses of KT-S (−) and IgG4-DS, but not KT-S (+).